There are a wide variety of materials used to fabricate wound dressings, which are used to treat a host of surgical and non-surgical lesions, such as burns and abrasions. The dressings range from simple gauze-type dressings to animal derived protein-type dressings such as collagen dressings, the composition of the particular dressing depends on the type of wound to be treated. Each of these dressings has advantages depending upon the type of application. For example, gauze-type dressings are sufficient and highly economical for simple abrasions and surgical incisions.
On the other hand, in cases of chronic wounds, polymer-based dressings are found to be more effective. By definition, chronic wounds are wounds that fail to proceed through the normal repair process and are typically manifestations of an underlying problem such as diabetes, venous disease or impaired circulation (Lazarus, G.S. et al., Definitions and Guidelines for Assessment of Wounds and Evaluation of Healing, Arch. Dermatology, vol. 130, pages 489-493, 1994). Thus, chronic wounds can be broadly categorized as pressure sores (decubitus), venous and diabetic ulcers depending on the underlying problem. Depending on the cause, various types of wound management treatments and materials are used to address the underlying problem and promote wound healing. Advanced polymeric materials with the capability of maintaining moist wound environment have been shown to be more effective than gauze in treating these difficult to heal chronic wounds.
Within the context of polymer-based dressings, various types of polymeric materials have been used in the treatment of skin disorders. Generally, they can be broken down into two major classes, namely synthetic and naturally derived polymeric materials.
Synthetic materials include polyurethanes, polyvinylpyrolidone (PVP), polyethyleneoxide (PEO), polyvinyl alcohol (PVA), and polyacrylonitrile (PAN). These materials may be used in combination with other synthetic or natural polymers to fabricate wound dressings with specific properties such as moisture retention and high fluid absorption. Both of these properties, generally not found in gauze-type dressings, promote healing by protecting chronic wounds from infection and maintaining moisture levels in the wound. Huang discloses in U.S. Pat. No. 6,238,691 a three dimensional crosslinked polyurethane hydrogel wound dressing, which is absorptive, contours to a wound site and maintains the wound in a moist state to promote healing.
Meyer-Ingold et. al. disclose in U.S. Pat. No. 6,156,334, wound coverings for the removal of interfering factors, such as antigens, free radicals, ions, proteins, peptides, lipids and free fatty acids, in the wound fluid of chronic wounds . These wound coverings are chemically modified with “trapper molecules”, such as antibodies, chelators, enzyme inhibitors, enzymes, enzyme mimics, peptides and other proteins, are polyurethane or plant-derived cellulose.
Similarly, naturally derived polymers or biopolymers, such as collagen and alginates, have also been used as wound dressings that exploit the desirable characteristics of the polymers, such as high absorption capacity of alginate or the biocompatible nature of collagen. Each of these dressings has associated particular advantages depending on the type of wound and amount of exudate it generates. However, these dressings also have disadvantages, which include higher cost, wound adherence, limited exudate absorption and residue deposition on a wound site.
Hydrocolloid dressings absorb wound exudate and provide a moist wound-healing environment, but also have the undesirable characteristic of residue deposition on a wound site. Additionally, unlike the microbial-derived cellulose dressing described herein, hydrocolloid dressings lack a moisture-donating feature necessary for dry chronic wounds with limited exudate. Also, hydrocolloids are known to adhere to the wound bed and can cause reinjury upon removal. Hydrocolloids have a tendency to break down in the wound bed possibly interfering with the wound healing process.
As an alternate material, microbial-derived cellulose possesses inherent characteristics which allow for effective promotion of wound healing without some of the inherent disadvantages associated with current wound dressings. In this regard, microbial-derived cellulose possesses the following physical properties that distinguish it from plant-derived cellulose such as extreme hydrophilicity and unique multi-layered three dimensional laminar structures that provide its moisture handling ability. Microbial cellulose is highly hydrophilic with a water-holding capacity ranging from 60 to 700 times its own weight as is described in U.S. Pat. No. 4,942,128. Microbial cellulose also demonstrates excellent wet strength and does not breakdown under compression. Lastly, because of its laminar multi-layered structure, microbial cellulose can be processed to produce a film with novel fluid handling ability. By adjusting the cellulose to liquid ratio, processed microbial cellulose is capable of both donating fluid or absorbing liquid depending on the surface the film is made to come in contact with.
Because of its superior characteristics, use of microbial cellulose in the medical industry has been previously investigated. For example, U.S. Pat. Nos. 4,588,400, 4,655,758 and 4,788,146 to Ring et al. disclose the possible use of microbial-derived cellulose in liquid-loaded medical pads. The patents to Ring et al focus on using statically produced microbial cellulose pads loaded with various liquids and medicaments. Various types of liquids that can be contained in the microbial cellulose pad were detailed as well as the production and cleaning method to produce the starting cellulose material. Also described in these patents are examples which detailed methods of fabrication of various pads wherein the method involves a series of pressing and soaking steps to adjust the physical properties, mainly with respect to the liquid to cellulose ratio to yield a desired product. As an example, these patents illustrate a highly hydrated pad (80 to 1 fluid to cellulose ratio) which is able to provide a cooling capability which is ideal for bum applications. In particular, the '146 patent describes the use of such liquid loaded pads as wet dressings for use as an ulcer dressing capable of providing moisture to the wound over an extended period of time. The same '146 patent also mentions that the wet dressings described in the examples also have the additional ability to absorb large quantities of fluid from the wound site when the dressing is applied in a less than saturated condition. However, the wound dressings of Ring et al. fail to mention a singular dressing having both the ability to be a source of moisture for chronic wounds as well as the ability to absorb fluid. The Ring et al. patents also fail to describe the effective liquid to cellulose ratio to fabricate a dressing having the dual fluid handing capability and also fail to disclose any particular benefits from the combination of microbial cellulose and an antimicrobial agent.
In particular, Ring fails to disclose levels of antimicrobial agents which would be non-irritating, non-cytotoxic and non-sensitizing. Additionally, Ring does not disclose which agents would be stable to gamma sterilization.
U.S. Pat. No. 4,912,049 to Farah et al. discloses the use of statically produced dehydrated microbial cellulose as an artificial skin graft, a separating membrane or artificial leather. The '049 patent recites the use of a cellulose film formed by Acetobacter xylinum that is dehydrated while it is stretched. Although the '049 patent described potential use of their invention as an artificial skin for treatment of wounds or injury, there is no suggestion that the material could be used for chronic wounds. Furthermore, the dried film of Farah has no moisture donation capability and minimal absorption capacity. Farah fails to disclose any particular benefit from the combination of microbial cellulose and an antimicrobial agent.
Finally, U.S. Pat. No. 5,846,213 by Wan et al. discloses methods of preparing microbial cellulose films using raw material produced in a stirred-tank bioreactor, instead of the static method. The '213 patent further describes the use of such cellulose material dissolved in solvents to fabricate membranes that can be use as wound dressings. Because of its dry nature of the resulting film, the cast material lacks any moisture donating ability and limited fluid absorption capacity. Also, the resulting cellulose membrane does not possess the three dimensional multi-layered structure found only in statically grown microbial cellulose as previously described. As with Ring et. al. and Farah, no disclosure of any particular benefit from the combination of microbial cellulose and an antimicrobial is made by Wan.
The use of additives in wound dressings to impart antimicrobial or inhibitory activity has been investigated. Silver based compounds (Arglaes and Acticoat dressings), chlorhexidine gluconate (Chlorhexidine Gauze Dressing BP), benzalkonium chloride (Band-Aid brand gauze dressing), parabens (NugelDressing), and PHMB (Kerlix and Excilon gauze dressings) have been incorporated into commercially available wound dressings in order to impart an antimicrobial or bioinhibitory property to the dressing. Ring in the '400 patent indicated in his claims the use of additives on liquid loaded medical pads made from microbial-derived cellulose , but failed to disclose any particular benefits from the combination of microbial cellulose and an antimicrobial agent. In particular, Ring fails to disclose levels of antimicrobial agents which would be non-irritating, non-cytotoxic and non-sensitizing. Additionally, Ring does not disclose which agents would be stable to gamma sterilization.
PHMB is a cosmetic preservative provided as a 20% solution in water under the trade name Cosmocil CQ. The use concentration in cosmetics is 0.2-1.0% of the 20% solution. The 20% concentrate is a strong irritant. Fifty thousand ppm was tolerated by rats, with no irritation. No sensitization was observed , in a guinea pig sensitization test. (Cosmetic and Drug Preservation: Principles and Practice, Ed. Jon J. Kabara. Marcel Dekker, Inc. New York and Basel. pp 728-730. 1984).
Brown described in U.S. Pat. No. 4,643,181 a surgical dressing or drape material coated with a solvent based contact adhesive, which contains polyhexamethylene biguanide hydrochloride dispersed therein.
Orr disclosed in U.S. Pat. No. 6,369,289 a cellulosic bandage consisting essentially of an antimicrobial amount of polyhexamethylene biguanide hydrochloride applied to the bandage, a method of covering an open wound with said bandage, and a method for the preparation of the same. The dressing described in Orr's '289 patent does not have the moisture donating capability demonstrated by the microbial-derived cellulose of the present invention.
In U.S. Pat. No. 4,655,756 Fawkes disclosed a non-woven material treated with a linear polymeric biguanide, preferably polyhexamethylene biguanide hydrochloride. The treated non-woven material is used to construct disposable nappies, which have reduced odor due to the antimicrobial activity of polyhexamethylene biguanide hydrochloride.
Quantrille in U.S. Pat. No. 4,837,079 discloses a non-woven web used as wet wipe containing polyhexamethylene biguanide hydrochloride, and a method for the preparation of the antimicrobial containing non-woven web. Unlike Fawkes, this invention produces a non-woven in which the polyhexamethylene biguanide hydrochloride is substantive to the web and binder. This substantive characteristic improves antimicrobial activity at lower concentrations and reduces irritation to users of the material.
Although the above patents recognize the potential use of microbial cellulose in medical applications, the prior art has failed to provide a method of developing a wound dressing which demonstrates effective wound healing, moisture management capability, antimicrobial activity, and adequate biocompatibility. Accordingly, an effective wound dressing comprising microbial cellulose for treatment of chronic wounds, which is highly biocompatible, is desirable. Furthermore, a wound dressing with high moisture donation and absorption capabilities is also particularly desirable for optimal wound healing. This dual moisture handling ability of the dressing of the present invention is capable of maintaining a moist wound environment necessary for healing chronic wounds. Also, the high moisture donation ability is particularly useful for treating dry necrotic tissue and promoting autolytic debridement that is desirable for any wound closure to be possible. Additionally, the ability of the wound dressing of the present invention in assisting autologous healing by promoting granulation and allowing epithelial cells to migrate exhibits the distinct ability of the wound dressing in effecting wound closure. Finally, the incorporation of an antimicrobial agent into the wound dressing will further enhance the healing process by combating or preventing microbial infections.
Thus, the present inventors have developed a wound dressing which possesses this novel fluid handling capability of absorption and donation. This fluid handling capability is an end result of the processing microbial cellulose to contain the proper cellulose content for the intended purpose. The resulting wound dressing can donate fluid if the wound surface is dry and found to be particularly useful for dry chronic wounds covered with dry necrotic tissue or eschar. The same dressing is also capable of absorbing fluid away from the exuding wound bed. Additionally, the microbial cellulose wound dressing described in this invention will not degrade and leave a residue in the wound site, unlike hydrocolloid dressings. Removal of the microbial cellulose dressing from the wound does not damage tissue because it does not adhere to the wound surface.
The present invention also envisages microbial cellulose sheets which can be directly synthesized in virtually any shape or size. Fermentation processes yield an extremely thin and pliable form, which is remarkably strong, yet, gas and liquid permeable. The shape will remain intact even when subjected to extreme environmental conditions such as autoclaving or gamma sterilization.